Description
SGC-GAK-1 (2226517-76-4) is a highly potent and selective inhibitor of cyclin G associated kinase (GAK), a member of the numb-associated kinase (NAK) family involved in membrane trafficking and sorting of proteins and is required for the maintenance of centrosome maturation and progression though mitosis. KD?= 1.9 nM with >50-fold selectivity against a panel of 400 kinases. It also displayed affinity for RIPK2 (KD?= 110 nM) and ADCK3 (KD?= 190 nM). SGC-GAK-1 displayed potent cellular activity in HEK293T cells (IC50?= 120 nM) and showed strong growth inhibition in the prostate cancer cell lines LNCaP (IC50?= 0.65 μM) and 22Rv1 (IC50?= 0.17 μM).
Uses
SGC GAK 1 is a high affinity cyclin G associated kinase (GAK) inhibitor (Kd = 1.9 nM). Exhibited >30-fold selectivity for GAK versus a panel of other kinases. Inhibits GAK in live cell assays (IC50 = 110 nM).
Biochem/physiol Actions
SGC-GAK-1 (CA93) is an ATP-competitive cyclin G-associated kinase (GAK) inhibitor (Ki = 3.1 nM by ATP site fluorescent tracer displacement assay; KD = 4.5 nM by ITC) that effectively inhibits Dengue viral entry and packaging in cultures (IC50 = 920 nM) without detectable cytotoxicity. SGC-GAK-1 exhibits much reduced affinity toward only 4 other kinases among a panel of ～400 (KD = 1.9 nM/GAK vs. 110 nM/RIPK2, 190 nM/ADCK3, 520 nM/NLK, 980 nM/AVCR1 by ligand competitive binding assay; IC50 = 110 nM/GAK vs. 360 nM/RIPK2 by cellular target engagement assay). SGC-GAK-1N (CA71) is a structure analog and the recommended negative control (GAK KD = 7.1 μM by ligand competitive binding assay; GAK & RIPK2 IC50 >50 μM by cellular target engagement assay). For characterization details of SGC-GAK-1, please visit the SGC-GAK-1 probe summary on the Structural Genomics Consortium (SGC) website.SGC-GAK-1N is the negative control for the active probe, SGC-GAK-1. SGC-GAK-1N is available from Sigma. To learn more about and purchase SGC-GAK-1N, click here.To learn about other SGC chemical probes, visit sigma.com/sgc
References
1) Asquith?et al.?(2019),?SGC-GAK-1: A Chemical Probe for Cyclin G Associated Kinase (GAK); J. Med. Chem.,?62?2830
